Abstract：
:Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule originating in the so-called L-cells of the intestine. The peptide has insulinotrophic properties and it is this characteristic that has predominantly been investigated. This has led to the use of the GLP-1-like peptide exendin-4 (EX-4), which has a much longer plasma half-life than GLP-1 itself, being used in the treatment of type II diabetes. The mode of action of this effect appears to be a reduction in pancreatic apoptosis, an increase in beta cell proliferation or both. Thus, the effects of GLP-1 receptor stimulation are not based upon insulin replacement but an apparent repair of the pancreas. Similar data suggest that the same effects may occur in other peripheral tissues. More recently, the roles of GLP-1 and EX-4 have been studied in nervous tissue. As in the periphery, both peptides appear to promote cellular growth and reduce apoptosis. In models of Alzheimer's disease, Parkinson's disease and peripheral neuropathy, stimulation of the GLP-1 receptor has proved to be highly beneficial. In the case of Parkinson's disease this effect is evident after the neurotoxic lesion is established, suggesting real potential for therapeutic use. In the present review we examine the current status of the GLP-1 receptor and its potential as a therapeutic target.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Harkavyi A,Whitton PSdoi
10.1111/j.1476-5381.2009.00486.xsubject
Has Abstractpub_date
2010-02-01 00:00:00pages
495-501issue
3eissn
0007-1188issn
1476-5381pii
BPH486journal_volume
159pub_type
杂志文章,评审abstract：:1. The mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701932
更新日期：1998-07-01 00:00:00
abstract：:1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07794.x
更新日期：1978-07-01 00:00:00
abstract：:1 Contractile responses produced by the alpha 1-adrenoceptor selective agonist, phenylephrine, and the alpha 2-adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta. 2 The relative order of potency of the agonists was noradr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09337.x
更新日期：1982-12-01 00:00:00
abstract：:The effects of carboxy-PTIO and hydroxocobalamin were studied on nitrergic transmission in anococcygeus and retractor penis muscles taken during post mortem examination from young male pigs. In both muscles under resting conditions, electrical field stimulation (EFS) caused contractions that were sensitive to tetrodot...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702496
更新日期：1999-05-01 00:00:00
abstract：:1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704260
更新日期：2001-09-01 00:00:00
abstract：:1. alpha 1-Adrenoceptor subtypes in rabbit thoracic aorta have been examined in binding and functional experiments. 2. [3H]-prazosin bound to two distinct populations of alpha 1-adrenoceptors (pKD,high = 9.94, Rhigh = 79.2 fmol mg-1 protein; pKD,low = 8.59, Rlow = 215 fmol mg-1 protein). Pretreatment with chloroethylc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13507.x
更新日期：1993-04-01 00:00:00
abstract：:1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pm...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702255
更新日期：1998-12-01 00:00:00
abstract：:1 The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied L-glutamic acid and DL-ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.2 Iontophoresis of L-glutamate to junctional sites produced transient depolarizat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb13675.x
更新日期：1979-06-01 00:00:00
abstract：:1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Wistar rats treated for 7 days with the adenosine antagonist, 1,3-dipropyl-8-sulphophenylxanthine (DPSPX), were examined. 2. Systolic blood pressure of the DPSPX-treated rats (164.0 +/- 2.9 mmHg; n = 6) was significantly greater than sali...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16683.x
更新日期：1995-09-01 00:00:00
abstract：:1. We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism. 2. Corneal epithelial migration was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702550
更新日期：1999-05-01 00:00:00
abstract：:1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13-didecanoate ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704434
更新日期：2002-01-01 00:00:00
abstract：:G protein-coupled receptors are the largest group of membrane proteins and are the targets for approximately 30% of drugs currently used therapeutically. These 7-transmembrane-spanning proteins continue to provide new opportunities to develop therapeutics based on emerging knowledge of their structure, signalling prop...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2010.00695.x
更新日期：2010-03-01 00:00:00
abstract：:Peroxisome proliferator activated receptors (PPAR)s are nuclear transcription factors of the steroid receptor super-family. One member, PPARgamma, a critical transcription factor in adipogenesis, is expressed in ECV304 cells, and when activated participates in the induction of cell death by apoptosis. Here we describe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703628
更新日期：2000-10-01 00:00:00
abstract：:The effect of trimetazidine (TMZ), an anti-anginal drug, on the mechanical response of the guinea-pig ductus arteriosus placed under conditions of mild hypoxia (PO2 approximately equal to 75 mmHg) was investigated. When the PO2 of the bathing solution was 75 mmHg, TMZ caused a dose-dependent increase in tension. The m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb12936.x
更新日期：1985-02-01 00:00:00
abstract：:Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the foll...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703886
更新日期：2001-03-01 00:00:00
abstract：:1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 mic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701373
更新日期：1997-09-01 00:00:00
abstract：:1. The atrioventricular node (AVN) is an important part of the conduction system in the heart and is a significant site of antiarrhythmic drug action. The class 1 antiarrhythmic propafenone is effective in treating a variety of arrhythmias, including those involving the AVN. In this study, we have investigated the eff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701086
更新日期：1997-05-01 00:00:00
abstract：:1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701564
更新日期：1997-12-01 00:00:00
abstract：:Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field pot...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10221.x
更新日期：1986-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The homeostatic control of arterial BP is well understood with changes in BP resulting from changes in cardiac output (CO) and/or total peripheral resistance (TPR). A mechanism-based and quantitative analysis of drug effects on this interrelationship could provide a basis for the prediction of dr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12190
更新日期：2013-08-01 00:00:00
abstract：:1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14127.x
更新日期：1990-11-01 00:00:00
abstract：:Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705641
更新日期：2004-02-01 00:00:00
abstract：:1. The effects of balloon injury on the reactivity of ipsilateral and contralateral carotid arteries were compared to those observed in arteries from intact animals (control arteries). 2. Carotid arteries were obtained from Wistar rats 2, 4, 7, 15, 30 or 45 days after injury and mounted in an isolated organ bath. Reac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705732
更新日期：2004-05-01 00:00:00
abstract：:1. The central and peripheral effects of the omega (benzodiazepine) site ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on intestinal myoelectrical activity were evaluated in conscious rats, chronically f...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16204.x
更新日期：1994-09-01 00:00:00
abstract：:1. We have investigated pre- and post-junctional responsiveness in vas deferens from wild-type and alpha(2A/D)-adrenoceptor knockout mice. The response to a single stimulus was not significantly different between wild-type and knock-out mice. The isometric contraction to 10 Hz stimulation for 4 s was significantly lar...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704791
更新日期：2002-07-01 00:00:00
abstract：:1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of chol...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb10471.x
更新日期：1981-11-01 00:00:00
abstract：:The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own geno...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14085
更新日期：2018-12-01 00:00:00
abstract：:In the last 20 years, the global regulatory frameworks for drug assessment have been managing the challenges posed by using cellular products as new therapeutic tools. Currently, they are defined as "Advanced Therapy Medicinal Products", comprising a large group of cellular types that either alone or in combination wi...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15305
更新日期：2020-11-03 00:00:00
abstract：:In ring preparations of the rabbit external jugular vein contracted with the thromboxane-mimetic U-46619, submicromolar concentrations of 5-hydroxytryptamine (5-HT) and chemically related analogues produced relaxations that were dependent on the integrity of the vascular endothelium. The receptor mediating endothelium...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb10287.x
更新日期：1987-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple or...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01098.x
更新日期：2011-02-01 00:00:00
